The overall goal of these studies is to establish cost-effective environmental conditions that support high standards of animal health and provide a comfortable, safe workplace. This application will test the animal health effects of changing animal husbandry procedures that are major sources of employee exposure to allergen. If these changes have no negative impact on animal health, instituting them should reduce allergen levels by more than 10-fold, and result in healthier workers and reduced animal care costs. By extrapolating the savings at TJL to all NIH-supported mouse care, the potential savings to NIH is $22 million a year. The first animal husbandry practice to be tested is housing animals in ventilated caging with cage pressure negative to the room and using enclosed negatively ventilated tables when changing cages. To measure allergen reduction, room and worker breathing zone allergen concentrations will be measured before and after the changes. Concern that cages with negative pressure might increase the transfer of pathogens among animals will be tested in an experimental animal room where infected mice will be isolated from other colonies. Transfer of Pneumocystis carinii from infected mice to pathogen-free immune-competent and immune-compromised mice will be monitored by several methods. The second animal husbandry change will be to reduce the frequency of cage changing from once every 7 days to once every 14 days. Allergen concentrations will be measured and compared for both changing schedules. The cage environment (ammonia, temperature, humidity) will be compared for each condition, and animal health will be assessed by reproductive performance, growth, immune system function, and by necropsy focused on the histology of the upper and lower respiratory systems of young mice. These studies will fill a number of gaps in scientific knowledge concerning the natural history of transmission of Pneumocystis among mice, and the harmful effects of ammonia in typical animal facilities where ammonia levels peak only for short times until bedding is changed or a litter is weaned. The use of mice naturally infected with P. carinii, Pasteurella pneumotropica and Helicobacter spp. will enable use of all three organisms in the negative pressure system.